Scoring mechanisms of p16INK4a immunohistochemistry based on either independent nucleic stain or mixed cytoplasmic with nucleic expression can significantly signal to distinguish between endocervical and endometrial adenocarcinomas in a tissue microarray study

<p>Abstract</p> <p>Background</p> <p>Endocervical adenocarcinomas (ECAs) and endometrial adenocarcinomas (EMAs) are malignancies that affect uterus; however, their biological behaviors are quite different. This distinction has clinical significance, because the appropriate therapy may depend on the site of tumor origin. The purpose of this study is to evaluate 3 different scoring mechanisms of p16^INK4aimmunohistochemical (IHC) staining in distinguishing between primary ECAs and EMAs.</p> <p>Methods</p> <p>A tissue microarray (TMA) was constructed using formalin-fixed, paraffin-embedded tissue from hysterectomy specimens, including 14 ECAs and 24 EMAs. Tissue array sections were immunostained with a commercially available antibody of p16^INK4a. Avidin-biotin complex (ABC) method was used for antigens visualization. The staining intensity and area extent of the IHC reactions was evaluated using the semi-quantitative scoring system. The 3 scoring methods were defined on the bases of the following: (1) independent cytoplasmic staining alone (Method C), (2) independent nucleic staining alone (Method N), and (3) mean of the sum of cytoplasmic score plus nucleic score (Method Mean of C plus N).</p> <p>Results</p> <p>Of the 3 scoring mechanisms for p16^INK4aexpression, Method N and Method Mean of C plus N showed significant (<it>p-values </it>< 0.05), but Method C showed non-significant (p = 0.245) frequency differences between ECAs and EMAs. In addition, Method Mean of C plus N had the highest overall accuracy rate (81.6%) for diagnostic distinction among these 3 scoring methods.</p> <p>Conclusion</p> <p>According to the data characteristics and test effectiveness in this study, Method N and Method Mean of C plus N can significantly signal to distinguish between ECAs and EMAs; while Method C cannot do. Method Mean of C plus N is the most promising and favorable means among the three scoring mechanisms.</p

Nuclear GRP75 Binds Retinoic Acid Receptors to Promote Neuronal Differentiation of Neuroblastoma

Retinoic acid (RA) has been approved for the differentiation therapy of neuroblastoma (NB). Previous work revealed a correlation between glucose-regulated protein 75 (GRP75) and the RA-elicited neuronal differentiation of NB cells. The present study further demonstrated that GRP75 translocates into the nucleus and physically interacts with retinoid receptors (RARα and RXRα) to augment RA-elicited neuronal differentiation. GRP75 was required for RARα/RXRα-mediated transcriptional regulation and was shown to reduce the proteasome-mediated degradation of RARα/RXRαin a RA-dependent manner. More intriguingly, the level of GRP75/RARα/RXRα tripartite complexes was tightly associated with the RA-induced suppression of tumor growth in animals and the histological grade of differentiation in human NB tumors. The formation of GRP75/RARα/RXRα complexes was intimately correlated with a normal MYCN copy number of NB tumors, possibly implicating a favorable prognosis of NB tumors. The present findings reveal a novel function of nucleus-localized GRP75 in actively promoting neuronal differentiation, delineating the mode of action for the differentiation therapy of NB by RA

Investigation of nonlinear wave-induced seabed response around mono-pile foundation

YesStability and safety of offshore wind turbines with mono-pile foundations, affected by nonlinear wave effect and dynamic seabed response, are the primary concerns in offshore foundation design. In order to address these problems, the nonlinear wave effect on dynamic seabed response in the vicinity of mono-pile foundation is investigated using an integrated model, developed using OpenFOAM, which incorporates both wave model (waves2Foam) and Biot’s poro-elastic model. The present model was validated against several laboratory experiments and promising agreements were obtained. Special attention was paid to the systematic analysis of pore water pressure as well as the momentary liquefaction in the proximity of mono-pile induced by nonlinear wave effects. Various embedment depths of mono-pile relevant for practical engineering design were studied in order to attain the insights into nonlinear wave effect around and underneath the mono-pile foundation. By comparing time-series of water surface elevation, inline force, and wave-induced pore water pressure at the front, lateral, and lee side of mono-pile, the distinct nonlinear wave effect on pore water pressure was shown. Simulated results confirmed that the presence of mono-pile foundation in a porous seabed had evident blocking effect on the vertical and horizontal development of pore water pressure. Increasing embedment depth enhances the blockage of vertical pore pressure development and hence results in somewhat reduced momentary liquefaction depth of the soil around the mono-pile foundation.Energy Technology Partnership (ETP), Wood Group Kenny, and University of Aberdeen; the National Science Fund for Distinguished Young Scholars (51425901) and the 111 project (B12032)

Investigation of Hepatoprotective Activity of Induced Pluripotent Stem Cells in the Mouse Model of Liver Injury

To date liver transplantation is the only effective treatment for end-stage liver diseases. Considering the potential of pluripotency and differentiation into tridermal lineages, induced pluripotent stem cells (iPSCs) may serve as an alternative of cell-based therapy. Herein, we investigated the effect of iPSC transplantation on thioacetamide- (TAA-) induced acute/fulminant hepatic failure (AHF) in mice. Firstly, we demonstrated that iPSCs had the capacity to differentiate into hepatocyte-like cells (iPSC-Heps) that expressed various hepatic markers, including albumin, α-fetoprotein, and hepatocyte nuclear factor-3β, and exhibited biological functions. Intravenous transplantation of iPSCs effectively reduced the hepatic necrotic area, improved liver functions and motor activity, and rescued TAA-treated mice from lethal AHF. 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate cell labeling revealed that iPSCs potentially mobilized to the damaged liver area. Taken together, iPSCs can effectively rescue experimental AHF and represent a potentially favorable cell source of cell-based therapy

Women with endometriosis have higher comorbidities: Analysis of domestic data in Taiwan

AbstractEndometriosis, defined by the presence of viable extrauterine endometrial glands and stroma, can grow or bleed cyclically, and possesses characteristics including a destructive, invasive, and metastatic nature. Since endometriosis may result in pelvic inflammation, adhesion, chronic pain, and infertility, and can progress to biologically malignant tumors, it is a long-term major health issue in women of reproductive age. In this review, we analyze the Taiwan domestic research addressing associations between endometriosis and other diseases. Concerning malignant tumors, we identified four studies on the links between endometriosis and ovarian cancer, one on breast cancer, two on endometrial cancer, one on colorectal cancer, and one on other malignancies, as well as one on associations between endometriosis and irritable bowel syndrome, one on links with migraine headache, three on links with pelvic inflammatory diseases, four on links with infertility, four on links with obesity, four on links with chronic liver disease, four on links with rheumatoid arthritis, four on links with chronic renal disease, five on links with diabetes mellitus, and five on links with cardiovascular diseases (hypertension, hyperlipidemia, etc.). The data available to date support that women with endometriosis might be at risk of some chronic illnesses and certain malignancies, although we consider the evidence for some comorbidities to be of low quality, for example, the association between colon cancer and adenomyosis/endometriosis. We still believe that the risk of comorbidity might be higher in women with endometriosis than that we supposed before. More research is needed to determine whether women with endometriosis are really at risk of these comorbidities

The violent youth of bright and massive cluster galaxies and their maturation over 7 billion years

In this study, we investigate the formation and evolution mechanisms of the brightest cluster galaxies (BCGs) over cosmic time. At high redshift (z ∼ 0.9), we selected BCGs and most massive cluster galaxies (MMCGs) from the Cl1604 supercluster and compared them to low-redshift (z ∼ 0.1) counterparts drawn from the MCXC meta-catalogue, supplemented by Sloan Digital Sky Survey imaging and spectroscopy. We observed striking differences in the morphological, colour, spectral, and stellar mass properties of the BCGs/MMCGs in the two samples. High-redshift BCGs/MMCGs were, in many cases, star-forming, late-type galaxies, with blue broad-band colours, properties largely absent amongst the low-redshift BCGs/MMCGs. The stellar mass of BCGs was found to increase by an average factor of 2.51 ± 0.71 from z ∼ 0.9 to z ∼ 0.1. Through this and other comparisons, we conclude that a combination of major merging (mainly wet or mixed) and in situ star formation are the main mechanisms which build stellar mass in BCGs/MMCGs. The stellar mass growth of the BCGs/MMCGs also appears to grow in lockstep with both the stellar baryonic and total mass of the cluster. Additionally, BCGs/MMCGs were found to grow in size, on average, a factor of ∼3, while their average Sérsic index increased by ∼0.45 from z ∼ 0.9 to z ∼ 0.1, also supporting a scenario involving major merging, though some adiabatic expansion is required. These observational results are compared to both models and simulations to further explore the implications on processes which shape and evolve BCGs/MMCGs over the past ∼7 Gyr

Measurement of the top quark forward-backward production asymmetry and the anomalous chromoelectric and chromomagnetic moments in pp collisions at √s = 13 TeV

Abstract The parton-level top quark (t) forward-backward asymmetry and the anomalous chromoelectric (d̂ t) and chromomagnetic (μ̂ t) moments have been measured using LHC pp collisions at a center-of-mass energy of 13 TeV, collected in the CMS detector in a data sample corresponding to an integrated luminosity of 35.9 fb−1. The linearized variable AFB(1) is used to approximate the asymmetry. Candidate t t ¯ events decaying to a muon or electron and jets in final states with low and high Lorentz boosts are selected and reconstructed using a fit of the kinematic distributions of the decay products to those expected for t t ¯ final states. The values found for the parameters are AFB(1)=0.048−0.087+0.095(stat)−0.029+0.020(syst),μ̂t=−0.024−0.009+0.013(stat)−0.011+0.016(syst), and a limit is placed on the magnitude of | d̂ t| &lt; 0.03 at 95% confidence level. [Figure not available: see fulltext.

Measurement of t(t)over-bar normalised multi-differential cross sections in pp collisions at root s=13 TeV, and simultaneous determination of the strong coupling strength, top quark pole mass, and parton distribution functions

Peer reviewe

ICAR: endoscopic skull‐base surgery

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